Search Results (3,833)

Hypoglycemia is associated with cardiovascular events reflected by platelet abnormalities. We hypothesized that sequential endothelial changes may occur during hypoglycemia that may enhance cardiovascular risk. In type 2 diabetes (T2D) (n = 23) and controls (n = 23), blood SOMAscan proteomic analysis of endothelial proteins at baseline, insulin-induced hypoglycemia and post hypoglycemia to 24 h were examined using repeated-measures linear mixed modeling with a prospective parallel study design. Most endothelial proteins that changed over time did not differ between groups. Baseline levels of P-selectin, plasminogen activator inhibitor-1 (PAI-1; serpine-1), E-selectin and angiopoietin-1 (ANGPT1) were significantly higher, whilst cadherin-5 was lower in T2D. Several proteins exhibited changes versus baseline in both T2D and controls. Under hypoglycemia, decreases in cadherin-5 and soluble angiopoietin-1 receptor (sTie-2) were observed, with increased P-selectin, intercellular adhesion molecule-3 (ICAM3), ANGPT1 and PAI-1. Post hypoglycemia, decreased cadherin-5 and ICAM5 were observed at 2 h and PAI-1 at 4 h, as well as increases in P-selectin at 30 min, 1 h and 24 h and ICAM3 at 24 h. Post hypoglycemia, E-selectin, P-selectin and ICAM3 were significantly lower in T2D patients at 2 h, while PAI-1 was significantly lower at 4 h and ICAM3 was significantly lower at 24 h. Baseline endothelial proteins differed between T2D and controls, which may suggest local endothelial inflammatory activation leading to a pro-thrombotic, destabilized vascular phenotype characteristic of diabetic vasculopathy. Hypoglycemia may exacerbate this towards a pro-adhesive and pro-thrombotic phenotype, worsening endothelial dysfunction. Full article

Background: Visceral adiposity has emerged as a clinically relevant determinant of early cardiometabolic dysfunction in pediatric type 1 diabetes mellitus (T1DM), yet its assessment remains underutilized in routine practice. This study evaluated ultrasonographically measured epicardial adipose tissue thickness (EATT) and perirenal adipose tissue thickness (PrATT) as markers of metabolic risk, insulin sensitivity, and subclinical atherosclerosis in children and adolescents with T1DM. Methods: This cross-sectional study included 150 participants with T1DM and 152 age- and sex-matched healthy controls. Anthropometric data, biochemical parameters, hepatic steatosis grade, and insulin sensitivity indices (eGDR) were collected. EATT and PrATT were measured via standardized echocardiographic and abdominal ultrasonographic protocols. Carotid intima–media thickness (cIMT) was assessed as an indicator of subclinical atherosclerosis. Correlation and multivariable logistic regression analyses were performed to identify independent predictors of T1DM status and cardiometabolic risk. Results: Children with T1DM exhibited significantly higher PrATT and EATT values compared with controls (both p < 0.05). All eGDR indices were markedly lower in the T1DM group, reflecting reduced insulin sensitivity. PrATT and EATT showed strong or moderate correlations with hsCRP, hepatic steatosis, atherogenic index of plasma, and multiple anthropometric markers. Both visceral fat depots were positively associated with cIMT. Logistic regression identified PrATT, EATT, hsCRP, cIMT, and eGDR-BMI as independent predictors of case status. Subgroup analyses demonstrated more pronounced visceral adiposity and metabolic impairment among participants with BMI ≥85th percentile. Conclusions: Ultrasonographically measured PrATT and EATT provide valuable insight into early cardiometabolic risk in youth with T1DM, independent of BMI. Their associations with insulin resistance, inflammation, and subclinical atherosclerosis highlight their potential utility as accessible markers for early risk stratification in pediatric diabetes. Routine incorporation of visceral fat assessment may support earlier identification of high-risk individuals and more targeted preventive strategies. Full article

The limitations of conventional diabetes management are increasingly evident. As a result, both type 1 and 2 diabetes in pediatric populations have become major global health concerns. As new technologies emerge, particularly artificial intelligence (AI), they offer new opportunities to improve diagnostic accuracy, treatment outcomes, and patient self-management. A PRISMA-based systematic review was conducted using PubMed, Web of Science, and BIREME. The research covered studies published up to February 2025, where twenty-two studies met the inclusion criteria. These studies examined machine learning algorithms, continuous glucose monitoring (CGM), closed-loop insulin delivery systems, telemedicine platforms, and digital educational interventions. AI-driven interventions were consistently associated with reductions in HbA1c and extended time in range. Furthermore, they reported earlier detection of complications, personalized insulin dosing, and greater patient autonomy. Predictive models, including digital twins and self-learning neural networks, significantly improved diagnostic accuracy and early risk stratification. Digital health platforms enhanced treatment adherence. Nonetheless, the barriers included unequal access to technology and limited long-term clinical validation. Artificial intelligence is progressively reshaping pediatric diabetes care toward a predictive, preventive, personalized, and participatory paradigm. Broader implementation will require rigorous multiethnic validation and robust ethical frameworks to ensure equitable deployment. Full article

In type 1 diabetes (T1D) in non-obese diabetic (NOD) mice, dendritic cells (DCs) exhibit a Stat5b mutation that impairs regulatory T cell (Tregs) numbers and suppressive function. To correct this defect, we generated transgenic NOD mice expressing constitutively active Stat5b (NOD.Stat5b-CA) in DCs, which conferred protection from diabetes that was associated with an expanded Treg population and a marked reduction in CD8⁺ T cell frequencies in secondary lymphoid organs. However, the phenotypic characteristics and underlying mechanisms to eliminate CD8⁺ T cells in NOD.Stat5b-CA mice are unknown. In this study, we found that the frequency of Tregs was significantly higher in the thymus and peripheral lymphoid organs of NOD.Stat5b-CA mice compared with NOD mice. Tregs in the peripheral lymphoid organs exhibited increased expression of activation markers CD69 and OX40, alongside reduced CD62L. We also found that CD8⁺ T cell frequencies were reduced in the peripheral organs but not in the thymus of NOD.Stat5b-CA mice, while CD4⁺ T cell frequencies remained unchanged across all organs. Furthermore, NOD.Stat5b-CA mice exhibited a reduced frequency of central Tregs (CD62L^high CD44^low) and increased frequency of effector Tregs (CD62L^low CD44^high) under steady-state conditions compared to NOD mice. Notably, Tregs from NOD.Stat5b-CA mice displayed enhanced cytotoxic activity, evidenced by increased expression of perforin, granzyme B, and Fas ligand, potentially mediating CD8⁺ T cell frequency reduction. Collectively, these findings highlight a novel role for Stat5b-CA.DC-educated Tregs in modulating immune responses by eliminating peripheral pathogenic CD8⁺ T cells via cytotoxic pathways, thereby contributing to immune regulation in NOD.Stat5b-CA mice. Full article

Background and Objectives: Despite substantial advances in treatment strategies for patients with type 2 diabetes mellitus (T2DM), its complication, particularly sarcopenia, has emerged as a global healthcare challenge. Pay-for-performance (P4P), an incentive-based payment scheme, has long been used to improve the quality of care; however, few studies have explored its effect on sarcopenia prevention. Therefore, we conducted a nested case–control study to investigate the association between P4P participation and the risk of sarcopenia among patients with T2DM. Materials and Methods: Using a large claims dataset, we identified individuals aged 20–70 years with newly diagnosed T2DM between 2001 and 2010 in Taiwan. All enrollees were followed up until 2013 to determine the occurrence of sarcopenia. For each case, we randomly matched two controls without sarcopenia. The risk of sarcopenia in relation to P4P participation was estimated by fitting conditional logistic regression to yield the adjusted odds ratio (aOR) and corresponding 95% confidence interval (CI). Results: A total of 3475 individuals with sarcopenia and 6948 matched controls were included. Patients enrolled in the P4P program had a lower risk of sarcopenia than their matched counterparts (aOR = 0.66; 95% CI: 0.61–0.74). Earlier P4P enrollment (within 1 year of T2DM diagnosis) and high-intensity P4P participation were associated with additional reductions in sarcopenia risk. Conclusions: Integrating P4P into routine T2DM care may help prevent sarcopenia, highlighting the importance of interdisciplinary collaboration and timely program implementation. Full article

This study successfully developed an oral vaccine for Type 1 Diabetes utilizing recombinant Lactococcus lactis expressing the GAD65 autoantigen. We conducted an in-depth investigation into its protective mechanisms in NOD mice, with a particular focus on its effects on the gut microbiota and metabolome. The administration of the GAD65-L. lactis vaccine resulted in a significant delay in diabetes onset and the preservation of pancreatic function. Our analyses revealed notable alterations in the gut microbial ecosystem, enhancing its diversity and the abundance of beneficial bacteria. Metabolomic profiling indicated time-dependent changes in metabolic pathways, with a marked enrichment of pyrimidine metabolism at 16 weeks and arachidonic acid metabolism at 24 weeks after vaccination by both GAD65-L. lactis and NZ9000-L. lactis. Integrated correlation analysis identified specific microbiota–metabolite interactions, including associations between Ruminiclostridium and lipid species in the GAD65-L. lactis group. These modifications in the microbial community and metabolic landscape were accompanied by enhanced immunoregulatory responses in intestinal LPLs, including expanded Treg populations and suppressed CD8⁺ T cells, a rising trend in IL-10-producing naive dendritic cells, and increased concentrations of TGF-β. Full article

Background/Objectives: Multidisciplinary hybrid educational programs combined with continuous glucose monitoring may contribute to improved self-management in adults with type 1 diabetes mellitus (T1DM); however, real-world evidence remains limited. This study assessed the effects of an educational intervention integrated with continuous glucose monitoring on glycemic control and patient-reported outcomes in adults with T1DM. Methods: We conducted a single-group quasi-experimental study including 210 adults with T1DM from a public hospital. The nurse-led hybrid intervention consisted of a 2-h in-person group educational session followed by an individual telematic follow-up session. All participants used continuous glucose monitoring. The primary outcome was the change in HbA1c at 9 months. Secondary outcomes included continuous glucose monitoring metrics, diabetes-related quality of life, treatment satisfaction, and hypoglycemia awareness. Results: HbA1c showed a statistically significant but modest reduction from 7.70 ± 1.10% to 7.45 ± 0.91% following the intervention (p = 0.003). No statistically significant changes were observed in continuous glucose monitoring metrics, including time in range, time below and above range, mean glucose, glycemic variability, or sensor wear time. In terms of emotional well-being, treatment satisfaction increased significantly (8.17 ± 7.86 vs. 12.73 ± 5.49; p < 0.001), and the Clarke score showed a statistically significant but modest decrease (2.49 ± 1.90 vs. 2.12 ± 1.88; p = 0.017). Although the overall quality of life score did not change significantly, statistically significant differences were observed in several subscales, including satisfaction, impact, and diabetes-related concern. Conclusions: A multidisciplinary hybrid educational intervention integrated with continuous glucose monitoring was associated with modest improvements in HbA1c and statistically significant, though limited, enhancements in quality of life, treatment satisfaction, and hypoglycemia awareness in adults with T1DM. These findings suggest that similar educational models may have a supportive role in routine care. Full article

Background/Objectives: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition that requires continuous glycemic monitoring to prevent acute and long-term complications. In recent years, Diabetic Alert Dogs (DADs) have been increasingly used as an adjunctive strategy to assist individuals with T1DM by alerting glycemic fluctuations through olfactory detection of physiological changes. Despite growing interest, the available evidence remains heterogeneous and fragmented. Methods: Therefore, this scoping review was conducted to address the following research question: “What evidence is available regarding the relationship between Diabetic Alert Dogs (DADs) and glycemic monitoring in individuals with T1DM?”, conducted in accordance with the Joanna Briggs Institute methodology and reported following the PRISMA Extension for Scoping Reviews. Results: Searches were performed in PubMed, Scopus, and Web of Science without time restrictions. After duplicate removal (n = 485), 2379 records were screened, of which 24 articles underwent full-text assessment and 10 studies met the predefined inclusion criteria. Regarding glycemic alteration detection, most studies (7/10) reported that DADs could identify both hypoglycemic and hyperglycemic episodes, while the remaining studies focused exclusively on hypoglycemia detection. Sensitivity values were consistently higher for hypoglycemia than for hyperglycemia, and none reported false alert rates exceeding 20%. In addition to glycemic alert performance, improvements in perceived safety, independence, and quality of life were described in half of the included studies (5/10). Conclusions: By systematically mapping the characteristics, outcomes, and methodological approaches of studies involving DADs, this scoping review provides an overview of current evidence and identifies key knowledge gaps in training protocols, outcome standardization, and performance reporting. Full article

Objectives: This study aimed to investigate the association between optical coherence tomography angiography (OCTA) parameters and cardiovascular (CV) risk scores in individuals with type 1 diabetes (T1D). Methods: A cross-sectional analysis of a large-scale prospective OCTA trial cohort (ClinicalTrials.gov NCT03422965) was performed. Demographic, systemic, and ocular data—including OCTA imaging—were collected. T1D participants were stratified into three CV risk categories: moderate (MR), high (HR), and very high risk (VHR). Individualized predictions for fatal and non-fatal CV events at 5 and 10 years were calculated using the STENO T1 Risk Engine calculator. Results: A total of 501 individuals (1 eye/patient; 397 T1D, 104 controls) were included. Subjects with MR (n = 37), HR (n = 152) and VHR (n = 208) exhibited significantly reduced vessel density (VD) (20.9 ± 1.3 vs. 20.2 ± 1.6 vs. 19.3 ± 1.8 mm⁻¹, p < 0.05), perfusion density (PD) (0.37 ± 0.02 vs. 0.36 ± 0.02 vs. 0.35 ± 0.02%, p < 0.05) and foveal avascular zone circularity (0.69 ± 0.06 vs. 0.65 ± 0.07 vs. 0.63 ± 0.09, p < 0.05). Statistically significant negative correlations were observed between CV risk and OCTA parameters including VD, PD, and retinal nerve fiber layer thickness, while central macular thickness (CMT) showed a positive correlation (p < 0.05). Notably, CMT was significantly associated with 5-year CV risk. Conclusions: OCTA-derived metrics, particularly reduced retinal VD and PD, are associated with elevated CV risk scores in T1D patients. These findings suggest that OCTA may serve as a valuable non-invasive tool for identifying individuals with increased CV risk scores. Full article

Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM), leading to sensory loss, balance disturbances, and an increased risk of ulcers and amputations. Early screening is crucial, and devices for measuring vibration perception threshold (VPT) play an important role in the timely detection and management of this condition. Objective: The aim of this systematic review was to evaluate the diagnostic accuracy and reliability of VPT measurement devices in individuals with DM. Methods: A systematic search was conducted in four databases, including studies that assessed the diagnostic accuracy and reliability of VPT measurement devices in patients with type 1 or type 2 DM, with VPT compared against reference standards for DPN, including nerve conduction studies (NCS) and clinical diagnosis. Cross-sectional and case–control studies were included. Risk of bias was assessed using the Quality Appraisal of Reliability (QAREL) tool and the JBI Critical Appraisal Checklist for Diagnostic Test Accuracy Studies. Results: Eighteen studies were analyzed. Most studies demonstrated moderate sensitivity and specificity and an acceptable level of reliability, with results varying according to technical and methodological factors. Conclusions: VPT measurement devices appear to be useful screening tools for detecting DPN; however, their diagnostic accuracy and reliability are not uniform and largely depend on technical and methodological factors. Standardized threshold values and measurement procedures, along with further research comparing the effectiveness of different protocols, are needed to improve clinical utility. Full article

Background/Objectives: The objective was to analyze the effects of Dipeptidyl Peptidase-4 (DPP-4) inhibitors on glycemic control, insulin dose, and preservation of β-pancreatic function (C-peptide) in patients with type 1 diabetes mellitus (T1DM). Methods: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with a search in the PubMed database. Five randomized clinical trials evaluating the use of different DPP-4 inhibitors in patients with T1DM were selected, measuring parameters including glycated hemoglobin (HbA1c), C-peptide, time in glycemic target/range (TIR), and daily insulin dose. Results: HbA1c showed significant reduction in some studies and no significant alterations in others. TIR increased in one study (~77.87% → ~84.40%). C-peptide showed variable effects across studies. The insulin dose did not show a substantial reduction. Conclusions: DPP-4 inhibitors demonstrated modest benefits for glycemic control and preservation of β-cell function in T1DM, but these effects were inconsistent due to methodological heterogeneity. Standardized studies are needed to define beneficial subgroups and long-term efficacy. Full article

Hypoglycaemia in patients with type 1 diabetes mellitus (T1DM) remains a major clinical burden and, beyond its metabolic complications, can cause serious cardiac arrhythmias. Multiple mechanisms lead to different types of arrhythmias during hypoglycaemia. However, existing studies often involve mixed diabetes populations, small cohorts, or limited monitoring during nocturnal periods, leaving a critical gap in understanding the links between glucose fluctuations and arrhythmic events. This review provides an updated combination of experimental and clinical evidence describing how autonomic dysfunction and ionic imbalances lead to electrophysiological instability and structural remodelling of the myocardium during hypoglycaemia. Continuous glucose monitoring (CGM) combined with electrocardiographic or wearable rhythm tracking may enable early detection of glycemic and cardiac disturbances and help identify high-risk individuals. Future prospective studies using combined CGM–ECG monitoring, particularly during sleep, are essential to clarify the relationship between hypoglycaemia and arrhythmic events. Full article

Timely recognition of type 1 diabetes (T1D) in children and adolescents is crucial to prevent acute complications such as diabetic ketoacidosis (DKA). This narrative review examines the pathophysiology, clinical presentation, and diagnostic challenges of childhood T1D, including the young age of onset, clinician training gaps, and overlapping symptomatology between T1D and other common pediatric illnesses. Despite increased awareness, a significant proportion of children still present with DKA at diagnosis due to misinterpretation of symptoms, such as polydipsia, polyuria, and weight loss. This work emphasizes the importance of early recognition, timely intervention, and the use of structured management algorithms for primary care clinicians. Strategies to reduce DKA incidence, based on existing literature, successful real-world examples, and current guidelines, include enhanced screening for high-risk populations, educational initiatives, and improved diagnostic protocols. By implementing systematic approaches and public health campaigns, healthcare providers can improve early T1D detection and prevent severe DKA complications, ultimately enhancing patient outcomes and reducing long-term morbidity. Full article

Background: Obesity is a worldwide public health problem, affecting organs and systems. It is also a cardiovascular risk factor, which facilitates the development of diseases, such as arterial hypertension, dyslipidemia, and diabetes, which are used as criteria for the diagnosis of metabolically unhealthy obesity. Objective: To analyze the association between blood pressure and metabolic health factors, stress level, and nutrient intake in overweight and obese university students through mediation analysis. Methods: A quantitative, non-experimental, cross-sectional, correlational, and quantitative study was conducted in a sample of 230 obese/overweight university students selected by a multistage mass random sampling method. To evaluate habitual dietary intakes, a CFCA food frequency questionnaire was applied; a DASS-21 scale was used to evaluate stress; blood pressure and anthropometric data were collected; insulin levels, lipid profile, and glucose were determined using fasting blood samples. Statistical analysis was performed using univariate methods (frequencies, trend, and dispersion measures) and a mediational model. Results: The majority were young people aged 18 years (18.7%), with morning and afternoon shifts (60%), overweight (76.1%), and obese (23.9%). Not all obese people have arterial hypertension; however, an increase in BMI increases the risk of suffering from this disease. Model 1 showed that certain types of stress and sex at birth have an important relationship with diastolic blood pressure, mediated in some cases by weight. In Model 2, weight is a significant mediator in the relationship between moderate stress and systolic BP, and between sex at birth and systolic BP, thus allowing us to contribute to the understanding of how these variables are interrelated. Conclusions: This suggests that severe stress and sex at birth not only affect BP directly, but also do so through their effect on weight. Thus, both pathways contribute to understanding the relationship between stress, sex at birth, and diastolic and systolic blood pressure. Nevertheless, the results of this study provide empirical knowledge to design evidence-based prevention and treatment strategies. Full article

Background: Type 2 diabetes mellitus (T2DM) is typically characterized by the dysregulation of metabolic remodeling. As a systemic metabolic disease, T2DM can affect the mass and function of skeletal muscle by inducing impaired energy metabolism, mitochondrial dysfunction, and chronic low-grade inflammation. β-Hydroxybutyrate dehydrogenase 1 (BDH1) is a rate-limiting enzyme involved in ketone body metabolism, and its activity is down-regulated in various models of diabetic complications. Aerobic exercise (AE) is recognized as an effective intervention to promote energy homeostasis and alleviate metabolic stress. Whether its protective effect on skeletal muscle in T2DM involves the regulatory control of BDH1 expression remains unclear. Methods: Wild-type (WT) and systemic BDH1 knockout (BDH1^−/−) male C57BL/6J mice were used to establish the sedentary control (SED) and AE models of T2DM by providing a high-fat diet combined with streptozotocin injection. The indicators related to metabolic remodeling were detected by hematoxylin and eosin staining, immunofluorescence staining, quantitative real-time PCR, and Western blot assays. Results: After 8 weeks of AE, we found that AE improved glycolipid metabolic disorders and mitochondrial quality control in the gastrocnemius muscle of T2DM mice by up-regulating BDH1, thereby alleviating oxidative stress, inflammation, and fibrosis. Compared with the WT mice, the BDH1^−/− T2DM mice in the SED group exhibited more severe phenotypic impairment. The metabolic improvement effect of AE was attenuated in the BDH1^−/− mice. Conclusions: BDH1 is a key effector enzyme that may mediate the AE-induced improvement in metabolic remodeling in the gastrocnemius muscle of mice with T2DM. Full article